Dexmedetomidine preconditioning activates pro-survival kinases and attenuates regional ischemia/reperfusion injury in rat heart

dc.contributor.authorIbacache, Mauricio
dc.contributor.authorSanchez, Gina
dc.contributor.authorPedrozo, Zully
dc.contributor.authorGalvez, Felipe
dc.contributor.authorHumeres, Claudio
dc.contributor.authorEchevarria, Ghislaine
dc.contributor.authorDuaso, Juan
dc.contributor.authorHassi, Mario
dc.contributor.authorGarcia, Lorena
dc.contributor.authorDiaz Araya, Guillermo
dc.contributor.authorLavandero, Sergio
dc.date.accessioned2024-01-10T12:04:54Z
dc.date.available2024-01-10T12:04:54Z
dc.date.issued2012
dc.description.abstractPharmacological preconditioning limits myocardial infarct size after ischemia/reperfusion. Dexmedetomidine is an alpha(2)-adrenergic receptor agonist used in anesthesia that may have cardioprotective properties against ischemia/reperfusion injury. We investigate whether dexmedetomidine administration activates cardiac survival kinases and induces cardioprotection against regional ischemia/reperfusion injury. In in vivo and ex vivo models, rat hearts were subjected to 30 min of regional ischemia followed by 120 min of reperfusion with dexmedetomidine before ischemia. The alpha(2)-adrenergic receptor antagonist yohimbine was also given before ischemia, alone or with dexmedetomidine. Erk1/2, Akt and eNOS phosphorylations were determined before ischemia/reperfusion. Cardioprotection after regional ischemia/reperfusion was assessed from infarct size measurement and ventricular function recovery. Localization of alpha(2)-adrenergic receptors in cardiac tissue was also assessed. Dexmedetomidine preconditioning increased levels of phosphorylated Erk1/2, Akt and eNOS forms before ischemia/reperfusion; being significantly reversed by yohimbine in both models. Dexmedetomidine preconditioning (in vivo model) and pen-insult protection (ex vivo model) significantly reduced myocardial infarction size, improved functional recovery and yohimbine abolished dexmedetomidine-induced cardioprotection in both models. The phosphatidylinositol 3-kinase inhibitor LY-294002 reversed myocardial infarction size reduction induced by dexmedetomidine preconditioning. The three isotypes of alpha(2)-adrenergic receptors were detected in the whole cardiac tissue whereas only the subtypes 2A and 2C were observed in isolated rat adult cardiomyocytes. These results show that dexmedetomidine preconditioning and dexmedetomidine pen-insult administration produce cardioprotection against regional ischemia/reperfusion injury, which is mediated by the activation of pro-survival kinases after cardiac alpha(2)-adrenergic receptor stimulation. (C) 2011 Elsevier B.V. All rights reserved.
dc.description.funderFondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT)
dc.description.funderFondo de Investigacion Avanzada en Areas Prioritarias (FONDAP)
dc.description.funderComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT), Santiago, Chile
dc.fechaingreso.objetodigital19-04-2024
dc.format.extent9 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.bbadis.2011.12.013
dc.identifier.eissn1879-260X
dc.identifier.issn0925-4439
dc.identifier.pubmedidMEDLINE:22230708
dc.identifier.urihttps://doi.org/10.1016/j.bbadis.2011.12.013
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/75907
dc.identifier.wosidWOS:000301885800006
dc.information.autorucMedicina;Echevarria G ;S/I;152736
dc.information.autorucMedicina;Ibacache M ;S/I;817
dc.issue.numero4
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final545
dc.pagina.inicio537
dc.publisherELSEVIER
dc.revistaBIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
dc.rightsacceso restringido
dc.subjectMyocardial ischemia
dc.subjectMyocardial infarction
dc.subjectAlpha2-adrenergic receptor
dc.subjectDexmedetomidine
dc.subjectAnesthesia
dc.subjectRECEPTOR SUBTYPES
dc.subjectMESSENGER-RNA
dc.subjectTRANSACTIVATION
dc.subjectEXPRESSION
dc.subjectRISK
dc.subjectREPERFUSION
dc.subjectAGONISTS
dc.subjectTISSUES
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDexmedetomidine preconditioning activates pro-survival kinases and attenuates regional ischemia/reperfusion injury in rat heart
dc.typeartículo
dc.volumen1822
sipa.codpersvinculados152736
sipa.codpersvinculados817
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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